The purpose of the work is to investigate mechanisms involved in the pathogenesis of several human diseases which have cutaneous manifestations, including pemphigus, epidermolysis bullosa dystrophica-recessive (EBD-r) and scleroderma. Our approach involves studying aspects of the cell biology and biochemistry of cultured whole human skin, human epidermal cells and dermal fibroblasts. Our experiments in pemphigus are directed towards defining the origin and specificities of the hydrolytic enzymes which are involved in producing the acantholytic cells and we are searching for agents which will inhibit the activity of these enzymes. We are engaged in determining the effects of other cell-surface agents such as burn serum autoantibodies, antibloodgroup antibodies and plant lectins on the histology of cultured human skin. We are working to characterize the pemphigus "antigen" from human epidermis and the components from pemphigus serum which bind the pemphigus autoantibody. We have studied cultured fibroblasts from patients with EBD-r and scleroderma for possible abnormalities in the qualitative and quantitative synthesis of collagen and glycosaminoglycans and for possible defects in the utilization and turnover of these major extracellular macromolecules. We have utilized components of the immune system in attempts to modulate rates of collagen synthesis by normal or scleroderma fibroblasts in vitro.